Condensation of aromatic ketones with carbohydrates and related materials



United States, Patent() CONDENSATION F AROMATIC KETONES WITH CARBOHYDRATES AND RELATED MATERIALS Carl B. Linn, Riverside, Ill., assignor, by mesne assignments, to Universal Oil Products Company, Des

Plaiues, Ill., a corporation of Delaware No Drawing. Application June 18, 1957 Serial No. 666,489

5 Claims. (Cl. 260345.9)

This application is a continuation-in-part of my copending application Serial No. 401,068, filed December 29, 1953, now Patent No. 2,798,079.

This invention relates to a process for interacting aromatic ketones with carbohydrates and materials closely related to carbohydrates. The process relates more particularly to the condensation of simple sugars, their desoxyand their omega-carboxy derivatives, compound sugars or oligosaccharides, and polysaccharides with aromatic ketones in the presence of a hydrogen fluoride catalyst.

An object of this invention is to produce organic materials suitable for use per se or as intermediates in the manufacture of detergents, pharmaceuticals, explosives, gelling agents, surface coatings, resins, and oxidation inhibitors by condensing aromatic ketones with carbohydrates or with carbohydrate derivatives.

One embodiment of this invention relates to a process which comprises condensing an aromatic ketone with a carbohydrate in the presence .of a hydrogen fluoride catalyst to produce a compound selected from the group consisting of an acylaryl-desoxy-alditol and an: acylaryldesoxy-ketitol, and recovering said resultant condensation product. 1

A specific embodiment of this invention relates to a process which comprises condensing acetophenone with glucose in the presence of a hydrogen fluoride catalyst to produce a l-(acetophenyl)-1-desoxy-glucitol, and recovering said resultant condensation product.

I have found that useful water-insoluble condensation products and also water-soluble condensation products are formed by reacting aromatic ketones with carbohydrates and related substances in the presence of a hydrogen fluoride catalyst. These reactions may be carried out in steel equipment or other suitable apparatus lined with silver, copper, and certain alloys such as Monel metal and the like. This treatment may be effected at temperatures of from about -40 C. to about 100, C. and preferably at temperatures of from about C. to about +50 C. The pressure at which the reaction is carried out will vary with the reaction temperature used and the mol fractions of reactants and hydrogen fluoride catalyst present. While many of the condensation reactions are carried out at substantially atmospheric pressure, it may be. desirable in certain instances and with certain reactants to carry out the reaction at pressures up to about 100 atmospheres or more. It is convenient in most instances to operate the equipment utilized at the pressure generated by the reaction mixture and the catalyst contained therein.

Aromatic ketones which may be. used as starting materials in the process of this invention may be represented by the following general formula:

in which R represents an aryl nucleus and R' is selected from the group consisting of alkyl, aryl, aralkyl, alkaryl,

cycloalkyl, etc.

These substituents R and R may also be substituted with various groupings such as carboxyl groups, sulfo groups, halogen atoms, etc. Examples of compounds which are included within the scope of this general formula are acetophenone, propiophenone, benzophenone, acetomesitylene, phenylglyoxal, benzylacetophenone, dypnone, dibenzoylmethane, benzopinacolone,

dimethylaminobenzophenone, acetonaphthalene, benzoy1- naphthalene, acetonaphthacene, benzoylnaphthacene, benzil, benzilacetophenone, ortho-hydroxyacetophenone, parahydroxyacetophenone, ortho hydroxy-para methoxyacetophenone, para-hydroxy-meta-methoxyacetophenone, zingerone, etc.

Carbohydrates which are condensed witharomatic ketones to form a compound selected from the group consisting of an acylaryl-desoXy-alditol and an acylaryldesoxy-ketitol include simple sugars, their desoxyand omega-carboxy derivatives, compound sugars or oligosaccharides, and polysaccharides.

Simple sugars include dioses, trioses, tetroses, pentoses, hexoses, heptoses, octoses, nonoses, and decoses. Cornpound sugars include disaccharides, trisaccharides, and tetrasaccharides. Polysaccharides include polysaccharides composed of only one type of sugar residue, polysaccharides composed of more than one type of sugar unit, polysaccharides composed of one type of uronic acid unit, i.e., polyuronides, polysaccharides composed of aldose (pentose orhexose) and uronic acid units, polysaccharides containing hexose units esterified with an inorganic acid, and polysaccharides containing amino sugar units.

Utilizable simple sugars include the diose, glycolaldehyde; trioses, such as glycerylaldehyde and s-dihydroxy- .acetone; tetroses, such as erythrose, threose, erythrulose, and apiose; the pentoses, such as arabinose; xylose, ribose, .lyxose, rhamnose (a methylpentose), fucose (a methyl pentose), rhodeose (a methylpentose), digitalose (a methoxymethylpentose), ketoxylose (a ketopentose), 2-desox-yribose and 2-desoxy-rnethylpentose (digitoxose); hexoses, such as mannose, glucose, idose, gulose, galactose, talose, allose, fructose, sorbose, tagatose, and psicose; hepto'ses, suchas glucoheptose, mannoheptose, galactoheptose, sedoheptose, mannoketoheptose, glucoheptulose,. and perseulose; octoses, such as glucooctose, mannooctos'e, and galactooctose; nonoses, such as glucononose,-and mannononose; and decoses such as glucodecose. Desoxy derivatives of simple sugars are formed by the replacement of a hydroxyl substituent in a sugar with hydrogen thereby forming a methyl or methylene linkage. The desoxypentoses and desoxyhexoses are the most commonly occurring of such compounds. The omega-carboxy derivatives of simple sugars, which are suitable in the process of the present invention include tartronic semialdehyde or its tautomer, hydroxypyruvic acid; .alpha-gamma-dihydroxyacetoacetic acid, threuronic'acid, 4-keto-2,3,S-trihydroxypentanoic acid, Xyluronic acid, 5-keto-tetrahydroxyhexanoic acids such as S-ketb-allonic acid, S-keto-gluconic acid, S-keto-mannonic acid, S-ketogulonic acid, and S-keto-galactonic acid; uronic acids containing 6 carbon atoms such as glucuronic acid, mannuronic acid, and galacturonic acid, and the 6-keto-penta hydroxyheptanoic acids. The simple sugars and their omega-carboxy derivatives, as starting materials for the process of this invention, may be represented by the following general formula:

+H0H). B in which A equals H and CH OH, n equals an integer a tautomer of hydroxypyruvic acid; when A=CH OH,

n=1, and B=H, the compound is s-dihydroxyacetone;

when A=CH OH, n=1, and B=CH OH, the compound -is erythrulose; when A=CH OH, n=l, and B=COOH, the compound is alpha-gamma-dihydroxyacetoacetic acid;

when A=H, n=2, and B=CH OH, the compound is erythrose or threose; when A=H, "=2, and B=COOH, the compound is threuronic acid; when A=CH OH, -'n=2, and B=CH OH, the compound is riboketose or .xyloketose; when A=CH OH, n=2, and B=COOH, the

compound is a 4-keto-2,3,S-trihydroxypentanoic acid;

:when A=H, n=3, and B=CH OH, the compound is "ribose, arabinose, xylose, or lyxose; when A=H, n=3.

and B=COOH, the compound is a 5 carbon atom uronic Lacid such as xyluronic acid; when A=CH OH, 11:3, -and B=CH OH, the compound is psicose, fructose,

sorbose, or tagatose; when A'=CH 0H, n' 3, and B=COOH, the compound is a S-keto-tetrahydroxyhexanoi'c acid; when A=H, n=4, and B=CH OH, the compound is allose, altrose, glucose, mannose, gulose, idose,

galactose, or talose; when A=H, n=4, and B=COOH,

glucuronic acid, mannuronic acid, and galacturonic acid; when A=CH OH, n=4, and B=CH OH, the compounds are heptoses; and when A=CH OH, n=4, and B=COOH,

the compounds are 6-ketopentahydroxyheptanoic acids.

The utilizable oligosacchrides or compound sugars :include disaccharides such as the pentose-hexose disaccharides including glucoapiose, vicianose and primeverose; the methylpentose-hexose disaccharides including glycorhamnoside, and rutinose; and the dihexoses 'such as turanose, maltose, lactose, cellobiose, gentiobiose, melibiose, sucrose, and trehalose. Other compound sugars are represented by trisaccharides such as the methylpentose-hexose saccharides including rhamninose and robinose; the trihexose saccharides including raflinose, melezitose, and gentianose. Anexample of a suitable tetrasaccharide is stachyose.

Various polysaccharides are also utilizable in the process of the present invention. These polysaccharides include pentosans such as araban, methylpentosans such as fucosan, and hexosans such as starch, cellulose, glycogen, inulin, mannan, galactan, lichenin, levan, dextran, and laminarin. Other polysaccharides which are composed of more than one type of sugar unit such as pentosans like'araboxylan, and the hexosans like galactoma'nnan may be used. Other utilizable polysaccharides are represented by those composed of uronic acid units and aldose units such as gum arabic, damson gum, gum tragacanth, linseed mucilage, and pectins, those composed of uronic acid units such as pectic acid and alginic acid, and those containing hcxose units esterified with an inorganic acid such as certain sea weed polysaccharides like agar.

The hydrogen fluoride catalyst which is used in this process may be used in anhydrous form or diluted with water to make a'hydrofluoric acid of the desired concentration. The hydrofluoric acid may also be further diluted with various inert diluents when it is desirable to operate the process of this invention with low hydrogen fluoride concentrations. Suitable inert diluents include the perfluoro derivatives of n-paraflinic hydrocarbons such as perfluoropropane, perfluoro-n-butane, perfluoro-npentane, perfiuoro-n-hexane, etc. Other suitable diluents are well known to those skilled in the art, for example, cycloparatfins such as cyclopeutane or cyclohexane may be utilized. In some instances, hydrofluoric acid of from about 85 to about 100% I- IF concentration is desirable,

the compound is a 6 carbon atom uronic acid such as and in some other instances it is most desirable to use anhydrous hydrogen fluoride as the catalyst.

The process may be carried out by slowly adding a hydrogen fluoride catalyst to a stirred mixture of arcmatic ketone and carbohydrate or related material being subjected to reaction while maintaining the reaction temperature at from about 40 to about 100 C. by suitable cooling and/ or heating means. It is often desirable or advisable to commingle the reactants and catalyst at relatively low temperatures such as from about C. to about -30 C. and then to permit the reaction mixture to warm gradually while the reactants and catalyst are stirred by suitable means such as a motor driven stirrer or other adequate mixing equipment. After the reaction has reached the desired degree of completion, the hydrogen fluoride catalyst is removed from the reaction mixture by distillation at atmospheric or lower pressures, or by 'passing'an inert gas through the reaction mixture while maintaining it at a relatively low temperature. Also the entire reaction mixture and catalyst may be mixed with water or may be added to ice'in order to quench the activity of the hydrogen fluoride catalyst and to permit separation of the organic reaction products and unreactedstarting 'materials from the catalyst. The organic reaction products may also be separated from aqueous hydrogen fluoride by means of an organic solvent such as ether, in which some of the organic material may be dissolved. Further means of isolating the reaction products are illustrated in the examples. Thus the product formed by reacting acetophenone with glucose or cellulose in the presence of substantially anhydrous hydrogen fluoride at 30 C. separated into an ethersoluble and water-insoluble product and an ether-insoluble and water-soluble product.

The process of this invention broadly emphasizes the reaction of carbohydrates including simple sugars, their derivatives, compound sugars, and polysaccharides with aromatic ketones using as a catalyst hydrogen fluoride. The type of product obtained is markedly affected by the length of time that the reactants are in contact with the hydrogen fluoride catalyst as well as the temperature of the reaction. The reaction products of this process lead to materials having diversified uses. For example, some of'the reaction products can be used per se as surface-coating materials as, for example, thermosetting resins whichcan be prepared simply by-heating. Resins can also be made by heating the reaction products with phenol, aniline, etc., and'combinations of the above compounds. Nitration of many of the reaction products will give explosives.- These explosives will contain nitro groups attached to the aromatic rings as well as being nitric acid esters or nitroalcohol derivatives. Various reaction products are eflective for gellingparaflinic or aromatic hydrocarbons. The products are'useful intermediates in the preparation of other organic compounds, for example, metal deactivators may be prepared by the reaction ofjthese compounds with a primary amine to yield a Schiffs base. The nature of this invention is illustrated further by the following examples, which however, should not be construed to limit unduly the generally broad scope of this invention.

Example I This example illustrates the reaction of an aromatic ketone, namely acetophenone, with a carbohydrate, namely" cellulose which is a polysaccharide containing glucoside linkages.

- An an example of the manner of conducting these experiments, the following detailed description is given: In a one liter steel turbomixer autoclave is sealed 41 grams of cellulose and 77 grams of acetophenone. With stirring, the autoclave is then cooled to 78 C. and

about 220 grams of hydlro'gen fluoride is added. The temperature is allowed to rise to 0 C. and the reactants are then-contacted at t is temperature for 36 hours.

Then, a stream of nitrogen is passed through the reactor at room temperature to remove most of the hydrogen fluoride. A substantial amount of hydrogen fluoride remains behind in the reaction mixture, although most of it can be removed by prolonging the nitrogen purge. The autoclave is opened and the product is found to be a heavy fuming brown syrup. This is then poured into a silver dish and depending upon the amount of hydrogen fluoride remaining therein weighs from about 130 to about 150 grams. After standing for several days in a hood-draft the product solidifies. This mass is then mascerated with large quantities of cold water to remove unreacted carbohydrate, if any. During the process, the cellulose is broken down into glucose residues which become soluble in cold water. The cold water insoluble portion of the product is treated with boiling water which after cooling and reduction in volume yields a chemical individual corresponding to 1,1 di (acetophenyl) l desoxy-glucitol of the following formula:

II HaC-C C-CHa CHaOH This experiment again illustrates the reaction of a carbohydrate, namely glucose, with an aromatic aldehyde. In this example 40 grams of glucose, 77 grams of acetophenone, and about 225 grams of hydrogen fluoride are utilized. The procedure utilized in this example is the same as that described hereinabove in Example 1 down through allowing the product to stand in a draft. To this crude product is added one liter of ethyl ether and the mixture is allowed to stand for two days. The ether is then decanted off and the residue is dissolved in 500 ml. of hot ethanol. The alcohol solution is filtered while hot, and is then allowed to stand at 0 C. The crystals which separate at this point are identified and correspond to the LI-di-(acetophenyD-l-desoxy-glucitol described in Example I.

The more soluble part of the product is believed to contain a mono-acetophenyl-glucitol corresponding to the following structural formula:

0 BIG- c H Example III stirred. Then, while continuing the stirring a stream of nitrogen is passed through the autoclave for about 3 hours. The reaction product is washed with several portions of cold water, and the cold water insoluble portion thereof is dissolved in boiling water. The hot aqueous solution is filtered and then set aside to cool. After standing for about 24 hours at 0 C., crystals of a chemical individual are recovered therefrom. This material after recrystallization is found to have the following structural formula:

0 0 II II o o 3 duo]; J HOH CHOH CHOH

Example IV In this example, starch is reacted with beta-acetonaphthalene. This experiment is carried out in asteel turbomixer autoclave as described in Example I, the charge being 109 grams of beta-acetonaphthalene, 40 grams of starch, and about 220 grams of hydrogen fluoride. The beta-acetonaphthalene and starch are sealed into the autoclave which is then cooled to about -40 C. at which temperature the hydrogen fluoride is added. The temperature of the autoclave is then allowed to rise to room temperature and is kept there for 24 hours time during which time the reaction mixture is stirred con tinually. Then, a stream of nitrogen is passed through the autoclave for about 6 hours. The reaction product is washed with several portions of water, then dissolved in boiling water. The hot aqueous solution is filtered, cooled, and set aside at 0 C. From this cooled filtrate a new chemical entity is recovered. After recrystallization from 50% ethanol a product is isolated of the following structural formula: I

I claim as my invention: 1. A process which comprises reacting an aromatic ketone having the general formula wherein R is an aryl nucleus and R is selected from the group consisting of alkyl, aryl, aralkyl, alkaryl and cycloalkyl, with a carbohydrate selected from the group consisting of monosaccharides, oligosaccharides, and polysaccharides, in the presence of hydrogen fluoride cata lyst at a temperature of from about 40 C. to about C.

2. A process which comprises reacting acetophenone with cellulose in the presence of hydrogen fluoride catalyst at a temperature of from about 40 C. to about 100 C.

3. A process which comprises reacting acetophenone with glucose in the presence of hydrogen fluoride catas 7 lyst at a temperature of from about -40 C. to about References Cited in the file of this patent 100 C.

4. A process which comprises reacting benzophenone UNITED STATES PATENTS with glucose in the presence of hydrogen fluoride c 2,252,725 Niederl Aug. 19, 1941 lyst at a temperature of from abo t 4 C- to about 5 2,798,079 Linn July 2,1957 100 C.

5. A process which comprises reacting beta-aceto- OTHER REFERENCES naphthalene with starch in the presence of hydrogen fiuoride catalyst at a temperature of from about 40 to Hackhs Chem Dlctlonary 3rd The Blakls' about 0 10 ton Co., Philadelphia (1944). 

1. A PROCESS WHICH COMPRISES REACTING AN AROMATIC KETONE HAVING THE GENERAL FORMULA 